An Introduction to Systems Biology: Design Principles of Biological Circuits
(2007)

Bernhard Ø. Palsson Cambridge U. Press, New York, 2006. $75.00 (322 pp.). ISBN 978-0-521-85903-5 Reviewed by Nigel Goldenfeld For some of us physicists, the recent explosion of interest in biology by our colleagues is something of a mystery— perhaps even a betrayal. Biology seems to offer none of the aesthetic elegance and beauty that is the hallmark of such cherished creations as the general theory of relativity and the standard model of strong, weak, and electromagnetic interactions. Neither does biology provide the breathtaking precision with which physical experiment and theory can agree in such phenomena as quantum electrodynamics or Josephson effects. And don’t even think about summarizing all of biology on a T-shirt; biology textbooks, unlike those for physics, generally describe reactions and structures in monstrous detail, without an equation in sight. So why the allure of the subject among physicists? And what meaningful contributions can physical scientists make to the field? One answer is the emergence of a new science of biological circuits, or systems biology, which has become advanced enough, both scientifically and promotionally, that textbooks are warranted. Uri Alon’s An Introduction to Systems Biology: Design Principles of Biological Circuits and Bernhard Ø. Palsson’s Systems Biology: Properties of Reconstructed Networks are two recent offerings by leaders in this new field. These texts deserve serious attention from any quantitative scientist or physicist who hopes to learn about modern biology. Both books are well written; each has a different focus. Thus they could be used together to create an accessible course for beginners, with the instructor’s choice of topics from each book. The books are a welcome departure from the typical biology textbook. First, they emphasize quantitative modeling rather than nomenclature; second, they concentrate on essentials of the modeling rather than on exhaustive lists of components that offer no meaningful integration; and third, the approaches described in the texts make nontrivial quantitative predictions that can be and have been verified. Alon’s book is the better place for physicists to start. It assumes no prior knowledge of or even interest in biology. Yet right from chapter 1 the author succeeds in explaining in an intellectually exciting way what the cell does and what degrees of freedom enable it to function. The book proceeds with detailed discussions of some of the key network motifs, circuitelement designs that are believed to be repeated over and over again in biological systems. Those motifs include autoregulation, feed-forward loops, positive-feedback loops, and kinetic proofreading. The discussions in all cases introduce the particular motif, use simple differential equations in most cases as a way to model it, and offer plenty of comparisons with experimental data. Alon does not forget to ask a question physicists obsess over: Are any general physical principles at work in biology? Alon does not overplay that point but has included a nice chapter on robustness. He focuses on concrete examples such as chemotaxis and developmental pattern formation. He also devotes a chapter to explaining the precision with which biological processes can so accurately identify the right molecules amidst a sea of potentially confusing “wrong” targets. The basis of this process is kinetic proofreading, a concept first presented by physicist John Hopfield, and one that is based on simple nonequilibrium kinetics. Alon ends his book with an epilogue on simplicity in biology. He draws the detailed strands together into an appealing and inspiring overview of biology. Without the preceding attention to biological detail, this exercise would be vacuous. One final aspect of An Introduction to Systems Biology that must be mentioned is the wonderful set of exercises that accompany each chapter. The exercises range from elementary to advanced research areas. For example, chapter 9 contains problems on the errorminimization capabilities of the genetic code, which I and several other physicists, including Alon, are still elucidating. I would have liked to see evolution play a more central role in the text—for example, in a chapter of its own that amplifies the important comments in the epilogue about the evolution of modularity. Perhaps when it’s time for the second edition, there will be enough concrete material to further justify including the topic. Palsson’s Systems Biology presents a completely different perspective. The book focuses less on principles and more on techniques for reconstructing detailed, elaborate, and predictive circuit models of biological systems. During the past 10 years these techniques have become feasible for entire organisms, thanks to the availability of fully sequenced genomes. It is now possible to map out the metabolic networks of bacteria such as Escherichia coli and simpler eukaryotes. However, other networks in organisms control other